The present invention is concerned with a novel process for the catalyzed isomerization of vitamin A compounds using nitrogen monoxide as the isomerization catalyst. In particular, the invention is concerned with the isomerization of undesired isomers of vitamin A compounds, e.g., the 9-Z-, 11-Z-, 9,13-di-Z- and 11,13-di-Z-vitamin A compounds individually or as a mixture of these isomers, into a corresponding mixture of the useful all-E- and 13-Z compounds, which are by necessity present in equilibrium.
In natural vitamin A, as is contained in many fish liver oils, e.g., shark, cod, halibut and Californian jewfish liver oil, the total content of vitamin A consists of about 65% of all-E vitamin A and about 35% of 13-Z-vitamin A. The all-E-vitamin A and its alkanoyl esters have, of all isomers, by far the highest biological activity and are accordingly almost exclusively used in human and animal nutrition. On the other hand, the 13-Z-vitamin A compounds also play an important role, namely as pharmaceutically active substances.
The vitamin A preparations commercialized at present are almost exclusively produced synthetically. Since the previously known and used processes for the production of a vitamin A compound do not yield pure all-E compound, but only mixtures of various isomers having more or less large amounts of the all-E isomer, there has hitherto always been the problem of the isomerization of the various undesired isomers to the all-E isomer. The problem is firstly to achieve yields of all-E compounds which are as high as possible and also--since the total Z.fwdarw.E conversion is not possible--to obtain mixtures from which the all-E isomer can be isolated in a manner which is as simple as possible.
The method most used previously was the isomerization with iodine in the presence of pyridine see, for example, German Auslegeschrift (DAS) 1 468 798!. The addition of pyridine is necessary in order to keep the formation of the 9-Z isomer as low as possible. However, this method has the disadvantage that the iodine must be removed as completely as possible from the reaction mixture after the isomerization and prior to the isolation of the all-E compound. This is usually carried out by the addition of an iodine reducing agent, such as, for example, sodium thiosulphate, sodium bisulphite or sodium borohydride, the excess of which is subsequently removed by washing, filtration or other suitable methods.
Photochemical isomerization using sensitizers is also known (see, for example, DAS 2 210 800). However, this method is encumbered with the disadvantage that the sensitizer must be removed after completion of the isomerization. Moreover, the photochemical isomerization (not only with, but also without sensitizers) requires complex and expensive special apparatuses, which can lead to considerable difficulties especially when working on an industrial scale.